Differentiating tumor heterogeneity in formalin‐fixed paraffin‐embedded (FFPE) prostate adenocarcinoma tissues using principal component analysis of matrix‐assisted laser desorption/ionization imaging mass spectral data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135165/1/rcm7776.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135165/2/rcm7776_am.pd

Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry for Therapeutic Drug Monitoring of Metformin and Rosuvastatin in Human Plasma

In this work a hydrophilic interaction liquid chromatography/positive ion electrospray mass spectrometric assay (HILIC/ESI-MS) has been developed and fully validated for the quantitation of metformin and rosuvastatin in human plasma. Sample preparation involved the use of 100 µL of human plasma, following protein precipitation and filtration. Metformin, rosuvastatin and 4-[2-(propylamino) ethyl] indoline 2 one hydrochloride (internal standard) were separated by using an X-Bridge-HILIC BEH analytical column (150.0 × 2.1 mm i.d., particle size 3.5 µm) with isocratic elution. A mobile phase consisting of 12% (v/v) 15 mM ammonium formate water solution in acetonitrile was used for the separation and pumped at a flow rate of 0.25 mL min−1 . The linear range of the assay was 100 to 5000 ng mL−1 and 2 to 100 ng mL−1 for metformin and rosuvastatin, respectively. The current HILIC-ESI/MS method allows for the accurate and precise quantitation of metformin and rosuvastatin in human plasma with a simple sample preparation and a short a chromatographic run time (less than 15 min). Plasma samples from eight patients were further analysed proving the capability of the proposed method to support a wide range of clinical studies

Determination of intact parabens in the human plasma of cancer and non-cancer patients using a validated fabric phase sorptive extraction reversed-phase liquid chromatography method with uv detection

Parabens have been widely employed as preservatives since the 1920s for extending the shelf life of foodstuffs, medicines, and daily care products. Given the fact that there are some legitimate concerns related to their potential multiple endocrine-disrupting properties, the development of novel bioanalytical methods for their biomonitoring is crucial. In this study, a fabric phase sorptive extraction reversed-phase liquid chromatography method coupled with UV detection (FPSE-HPLC-UV) was developed and validated for the quantitation of seven parabens in human plasma samples. Chromatographic separation of the seven parabens and p-hydroxybenzoic acid was achieved on a semi-micro Spherisorb ODS1 analytical column under isocratic elution using a mobile phase containing 0.1% (v/v) formic acid and 66% 49 mM ammonium formate aqueous solution in acetonitrile at flow rate 0.25 mL min−1 with a 24-min run time for each sample. The method was linear at a concentration range of 20 to 500 ng mL−1 for the seven parabens under study in human plasma samples. The efficiency of the method was proven with the analysis of 20 human plasma samples collected from women subjected to breast cancer surgery and to reconstructive and aesthetic breast surgery. The highest quantitation rates in human plasma samples from cancerous cases were found for methylparaben and isobutylparaben with average plasma concentrations at 77 and 112.5 ng mL−1 . The high concentration levels detected agree with previous findings for some of the parabens and emphasize the need for further epidemiological research on the possible health effects of the use of these compounds

A Comparative Study of Hollow Copper Sulfide Nanoparticles and Hollow Gold Nanospheres on Degradability and Toxicity

Gold and copper nanoparticles have been widely investigated for photothermal therapy of cancer. However, degradability and toxicity of these nanoparticles remain concerns. Here, we compare hollow CuS nanoparticles (HCuSNPs) with hollow gold nanospheres (HAuNS) in similar particle sizes and morphology following intravenous administration to mice. The injected pegylated HCuSNPs (PEG-HCuSNPs) are eliminated through both hepatobiliary (67 percentage of injected dose, %ID) and renal (23 %ID) excretion within one month postinjection. By contrast, 3.98 %ID of Au is excreted from liver and kidney within one month after iv injection of pegylated HAuNS (PEG-HAuNS). Comparatively, PEG-HAuNS are almost nonmetabolizable, while PEG-HCuSNPs are considered biodegradable nanoparticles. PEG-HCuSNPs do not show significant toxicity by histological or blood chemistry analysis. Principal component analysis and 2-D peak distribution plots of data from matrix-assisted laser desorption ionization-time-of-flight imaging mass spectrometry (MALDI-TOF IMS) of liver tissues demonstrated a reversible change in the proteomic profile in mice receiving PEG-HCuSNPs. This is attributed to slow dissociation of Cu ion from CuS nanoparticles along with effective Cu elimination for maintaining homeostasis. Nonetheless, an irreversible change in the proteomic profile is observed in the liver from mice receiving PEG-HAuNS by analysis of MALDI-TOF IMS data, probably due to the nonmetabolizability of Au. This finding correlates with the elevated serum lactate dehydrogenase at 3 months after PEG-HAuNS injection, indicating potential long-term toxicity. The comparative results between the two types of nanoparticles will advance the development of HCuSNPs as a new class of biodegradable inorganic nanomaterials for photothermal therapy

Editorial for Special Issue “Sample Preparation-Quo Vadis: Current Status of Sample Preparation Approaches-2nd Edition”

Sample preparation is and will always be the most important step in chemical analysis [...

Quantitation of Acetyl Hexapeptide-8 in Cosmetics by Hydrophilic Interaction Liquid Chromatography Coupled to Photo Diode Array Detection

Bioactive peptides are gaining more and more popularity in the research and development of cosmetic products with anti-aging effect. Acetyl hexapeptide-8 is a hydrophilic peptide incorporated in cosmetics to reduce the under-eye wrinkles and the forehead furrows. Hydrophilic interaction liquid chromatography (HILIC) is the separation technique of choice for analyzing peptides. In this work, a rapid HILIC method coupled to photodiode array detection operated at 214 nm was developed, validated and used to determine acetyl-hexapeptide-8 in cosmetics. Chromatography was performed on a Xbridge® HILIC BEH analytical column using as mobile phase a 40 mM ammonium formate water solution (pH 6.5)-acetonitrile mixture 30:70, v/v at flow rate 0.25 mL min−1. The assay was linear over the concentration range 20 to 30 μg mL−1 for the cosmetic formulations and 0.004 to 0.007% (w/w) for the cosmetic cream. The limits of quantitation for acetyl hexapeptide-8 were 1.5 μg mL−1 and 0.002% (w/w) for the assay of cosmetic formulations and cosmetic creams, respectively. The method was applied to the analysis of cosmetic formulations and anti-wrinkle cosmetic creams

Assessment of molecular differentiation in FFPE colon adenocarcinoma tissues using PCA analysis of MALDI IMS spectral data

MALDI IMS datasets comprise huge amounts of spectra and their interpretation requires the use of multivariate statistical methods. MALDI IMS spectral data have been processed using sequential principal component analysis and 2-D peak distribution tests so as to investigate the molecular differentiation of tumor regions in formalin-fixed paraffin-embedded tissue biopsies of colorectal adenocarcinoma. In some of the cases fresh frozen tissue section samples were also analyzed for comparison. Multivariate analysis of spectral data revealed a specific pattern of mass ion peaks in different tumor regions that were distinguishable from the adjacent normal regions within a given specimen. Moreover, similar mass ion peaks could be detected in both FFPE and fresh-frozen tissue section samples. These significant mass ion peaks have been used to generate ion images and visualize the difference between tumor and normal regions. These specific and statistically significant ion peaks may serve as potential biomarkers for colorectal adenocarcinoma

Dietary Exposure Assessment of Veterinary Antibiotics in Pork Meat on Children and Adolescents in Cyprus

In recent years, huge amounts of antibiotics have been administered to farm animals, and as a result, residues of these antibiotics can accumulate in livestock products and, once consumed, may be transmitted to humans. Farm animals’ antibiotic treatment may therefore present a risk for consumers health, especially for children and adolescents. In children, the immune system is not fully developed, and thus, they are more susceptible than adults to resistant bacteria. A dietary exposure assessment was conducted on veterinary antibiotics found in raw pork meat among children and adolescents in Cyprus, since pork is the most consumed red meat in Cypriot population. The study was based on the results of the occurrence of 45 residual antibiotics in raw pork meat samples in Cyprus between 2012 and 2017 in combination with data on the consumption of pork meat on children and adolescents taken from the latest demographic report in Cyprus. Estimated daily intake (EDI) values of veterinary antibiotics for children aged 6–9 years old, were higher compared to EDI values for adolescents aged 10–17 years old. The percentage ratio of the estimated daily intake to the acceptable daily intake for all the veterinary antibiotic residues was less than 5.6. The results indicate that antibiotic residues in pork meat of inland production are below the acceptable daily intake and are of low risk to human health related to the exposure of antibiotics. Nevertheless, continuous exposure to low levels of antibiotic residues in respect to age vulnerability should be of a great concern